The Bovini tribe of the Bovidae family occupy a unique and important role in human history. Members of this group have been domesticated since at least the early Neolithic period with modern cattle being the most prominent example. Members of this group provide valuable economic contributions including the production of meat, dairy products and leather. As of Jan. 1, 2011, the US Department of Agriculture estimated that the US inventory was 92.6 million head of cattle. In 2010, US farmers produced more than 26 billion pounds of beef valued at an estimated $37 billion. The USDA estimated that the retail equivalent value of the US beef industry in 2010 was $74 billion. The Bovini tribe, particularly cattle, are an important part of the American farm economy.
Disease can have a significant negative impact on herds resulting in large economic losses. Disease can cause premature culling of infected animals, increased veterinary costs, increased susceptibility to further disease, breeding problems, decreased milk production, decreased slaughter value, and decreased feed efficiency. Additionally, disease agents can enter into food supply when the animals are harvested and processed. This can cause expensive recalls of potentially contaminated food products. As such, the control of disease causing agents is of particular concern in the farming industry.
One class of disease causing agents is the Enterobacteriaceae family of Gram-negative bacteria. While some members of this family are harmless symbionts or commensals, serious and familiar pathogens such as Salmonella, Escherichia coli, Yersinia, Klebsiella, Shigella, Proteus, Enterobacter, Serratia, and Citrobacter are also included. Infections with these pathogenic bacteria can result in diseases such as diarrhea, pneumonia, sepsis, hemorrhagic colitis, and hemolytic-uremic syndrome.
In order to control outbreaks of disease, a number of preventative measures are employed. These measures include culling affected animals, manure management programs, sterilization of instruments, vaccination, and the use of antibiotics. While these approaches are effective at reducing the rate of infection, the techniques can result in additional issues. For example, the regular use of antibiotics in herds has resulted in pathogens which are resistant to common antibiotics—a phenomenon which increases the difficulty of treating the disease and which poses a larger health risk. As such, there is a need in the art for new and additional approaches to increase Bovini resistance to Enterobacteriaceae.
The inventors have developed a novel approach for increasing such resistance in bovine subjects. Specifically, the inventors have developed a method of increasing resistance to Enterobacteriaceae by identifying genetic traits (high-affinity microRNA-binding sites in 3′ untranslated regions) that decrease the expression of bovine proteins interacting with Enterobacteriaceae, using the protein designated as Synaptojanin 1 as the paradigm.
It is an object of the present invention to provide the molecular basis for increasing the resistance of a bovine subject to Enterobacteriaceae.
It is a further object of the present invention to provide bovine subjects and herds of bovine subjects with increased resistance to Enterobacteriaceae.
It is a further object of the present invention to provide materials for artificial insemination of bovine subjects, specifically semen, which can be used to produce bovine subjects and herds of bovine subjects which exhibit increased resistance to Enterobacteriaceae.
It is a further object of the present invention to provide a genetic test for determining a bovine subject's likely resistance to Enterobacteriaceae.
It is yet another object of the invention to provide further information for understanding and changing a bovine subject's resistance to Enterobacteriaceae.
It is yet another object of the present invention to use the above information to identify other mutations in linkage disequilibrium with or that are causative of differences in resistance to Enterobacteriaceae in specific lines, populations, or breeds of cattle.
Other objects will become apparent from the detailed description of the invention which follows.